- Rhodium(III)-Catalyzed Alkynylation of 4-Arylphthalazin-1(2H)-one Scaffolds via C-H Bond Activation
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Selective C–H bond alkynylation toward modular access to material and pharmaceutical molecules is of great desire in modern organic synthesis. Disclosed herein is rhodium(III)-catalyzed selective C–H bond mono-/bialkynylation of 4-aryl phthalazin-1(2H)-one was developed. The silver salt AgSbF6 are demonstrated to play a vital role in promoting the bialkynylation reactions. The present alkynylation strategy is simple, efficient, and features high functional group tolerance and broad substrate scope under an air atmosphere. Additionally, 6-aryl pyridazin-3(2H)-one scaffold is amenable to the selective monoalkynylation and sequential bialkynylation, respectively.
- Du, Xuxin,Hou, Hongcen,Zhao, Yongli,Sheng, Shouri,Chen, Junmin
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supporting information
p. 1100 - 1107
(2020/02/25)
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- A new series of pyridazinone derivatives as cholinesterases inhibitors: Synthesis, in vitro activity and molecular modeling studies
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Background: The pyridazinone nucleus has been incorporated into a wide variety of therapeutically interesting molecules to transform them into better drugs. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known to be serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh). Inhibition of cholinesterases is an effective method to curb Alzheimer's disease. Here, we prepared 12 new 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(nonsubstituted/4-substituted benzenesulfonohydrazide) derivatives and evaluated their inhibitory effects on AChE/BChE in pursuit of potent dual inhibitors for Alzheirmer's Disease. We also tried to get insights into binding interactions of the synthesized compounds in the active site of both enzymes by using molecular docking approach. Method: We obtained our compounds by the reaction of various substituted/nonsubstituted benzenesulfonic acid derivatives with 6-substitutedphenyl-3(2H)-pyridazinone-2-yl acetohydrazide and determined their anticholinesterase activities according to the Ellman's method. Molecular docking studies were done using Glide and the results were evaluated on Maestro (Schr?dinger, LLC, New York, NY, 2019). Results: The title compounds showed moderate inhibition at 100 μg/ml against both enzymes, yet with better activity against BChE. Compound VI2a emerged as a dual inhibitor with 25.02% and 51.70% inhibition against AChE and BChE, respectively. Conclusion: This study supports that novel pyridazinone derivates may be used for the development of new BChE inhibitory agents. It was less potent than the reference drugs, yet promising for further modifications as a lead. The ability of the compounds to adopt energetically more favourable conformations and to engage in more key interactions in the ECBChE active gorge explains their better activity profile against ECBChE.
- ?z?elik, Azime Berna,?zdemir, Zeynep,Sari, Suat,Utku, Semra,Uysal, Mehtap
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p. 1253 - 1263
(2019/11/03)
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- Features of reactions of (E)-[(2-aroyl)ethenyl]triphenylphosphonium bromides with binucleophiles
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Reactions of (E)-[(2-aroyl)ethenyl]triphenylphosphonium bromides with hydroxylamine hydrochloride resulted in the formation of oximes undergoing α-phenyl migration when reacted with aqueous alkali. Reaction of these salts with hydrazine hydrochloride and
- Khachikyan, R. Dzh.,Ovakimyan,Panosyan,Tamazyan,Ayvazyan
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p. 1503 - 1509
(2017/09/01)
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- Synthesis and Bioevaluation of 3,6-Diaryl-[1,2,4]triazolo[4,3-b] Pyridazines as Antitubulin Agents
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A series of 3,6-diaryl-[1,2,4]triazolo[4,3-b]pyridazines were designed as a class of vinylogous CA-4 analogues. The easily isomerized (Z,E)-butadiene linker of vinylogous CA-4 was replaced by a rigid [1,2,4]triazolo[4,3-b]pyridazine scaffold. Twenty-one target compounds were synthesized and exhibited moderate to potent antiproliferative activity. The compound 4q with a 3-amino-4-methoxyphenyl moiety as the B-ring, comparable to CA-4 (IC50 = 0.009-0.012 μM), displayed the highly active antiproliferative activity against SGC-7901, A549, and HT-1080 cell lines with IC50 values of 0.014, 0.008, and 0.012 μM, respectively. Tubulin polymerization experiments indicated that 4q effectively inhibited tubulin polymerization, and immunostaining assay revealed that 4q significantly disrupted tubulin microtubule dynamics. Moreover, cell cycle studies revealed that compound 4q dramatically arrested cell cycle progression at G2/M phase in A549 cells. Molecular modeling studies showed that 4q could bind to the colchicine binding site on microtubules.
- Xu, Qile,Wang, Yueting,Xu, Jingwen,Sun, Maolin,Tian, Haiqiu,Zuo, Daiying,Guan, Qi,Bao, Kai,Wu, Yingliang,Zhang, Weige
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supporting information
p. 1202 - 1206
(2016/12/18)
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- Copper-catalyzed aerobic dehydrogenation of C-C to C=C bonds in the synthesis of pyridazinones
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A simple and efficient procedure for the synthesis of pyridazin-3(2H)-ones through copper-catalyzed dehydrogenation of a single C-C bond of 4,5-dihydropyridazin-3(2H)-ones to a C=C bond with oxygen as the terminal oxidant is described. Functional groups including hydroxy, carboxylic, bromo, chloro, cyano, nitro and alkoxy were all tolerated under the reaction conditions. Moreover, this methodology was applied to the preparation of a series of structurally similar N-substituted 6-phenylpyridazinone compounds containing fluorine. The dehydrogenation reactions exhibit good yields and selectivity. Copper-catalyzed dehydrogenation of a C-C bond of 4,5-dihydropyridazinones to a C=C bond with oxygen as the terminal oxidant is described. Various functional groups were tolerated under the reaction conditions. The method was also applied to the preparation of a series of N-substituted 6-phenylpyridazinones containing fluoride. The dehydrogenation reactions exhibit good yields and selectivity.
- Liang, Lei,Yang, Guanyu,Xu, Fengrong,Niu, Yan,Sun, Qi,Xu, Ping
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supporting information
p. 6130 - 6136
(2013/09/24)
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- Reactions of 3-aroylacrylates with α-aminoazoles
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Dihydro derivatives of pyrazolo[3,4-b]pyridine-, pyrazolo[1,5-a]pyrimidine- , and [1,2,4]triazolo-[1,5-a]pyrimidinecarboxylates have been prepared by cyclocondensation of β-aroylacrylates with 5-aminopyrazoles and 3-amino-1,2,4-triazole. Heating dihydro[1,2,4]triazolo[1,5-a]pyrimidine-7- carboxylates with hydrazine hydrate led to recyclization of the pyrimidine ring to form 6-arylpyridazin-3(2H)-ones.
- Kolos,Kovalenko,Borovskoy
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p. 983 - 988
(2012/02/16)
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- Synthesis of some new pyridazin-3-one derivatives and their utility in heterocyclic synthesis
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(Chemical Equation Presented) Synthesis of new heterocyclic compounds containing the pyridazinone moiety, which have a valuable biological activities, has been achieved through the nucleophilic addition of benzylamine to 4-(p-substituted phenyl)-4-oxo-2-b
- El-Mobayed, Medhat M.,Hussein, Ahmed M.,Mohlhel, Wafia M.
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experimental part
p. 534 - 537
(2010/09/05)
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- FUSED BICYCLOHETEROCYCLE SUBSTITUTED QUINUCLIDINE DERIVATIVES
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Compounds of formula (I) wherein n is 0, 1, or 2; A is N or N+-O-; X is O, S, -NH-, and -N-alkyl-; Ar1 is a 6-membered aromatic ring; and Ar2 is a fused bicycloheterocycle. The compounds are useful in treating conditions or disorders prevented by or ameliorated by a7 nAChR ligands. Also disclosed are pharmaceutical compositions having compounds of formula (I) and methods for using such compounds and compositions.
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Page/Page column 75-76
(2010/11/08)
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- Substituted diazabicycloalkane derivatives
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Compounds of formula (I) [in-line-formulae]Z-Ar1—Ar2??(I) [/in-line-formulae] wherein Z is a diazabicyclic amine, Ar1 is a 5- or 6-membered aromatic ring, and Ar2 is selected from the group consisting of an unsubstituted or substituted 5- or 6-membered heteroaryl ring; unsubstituted or substituted bicyclic heteroaryl ring; 3,4-(methylenedioxy)phenyl; carbazolyl; tetrahydrocarbazolyl; naphthyl; and phenyl; wherein the phenyl is substituted with 0, 1, 2, or 3 substituents in the meta- or para-positions. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions comprising compounds of formula (I) and methods for using such compounds and compositions.
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Page/Page column 42
(2010/02/11)
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- 3-Quinuclidinyl amino-substituted biaryl derivatives
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Compounds of formula (I) wherein A is N or N+—O?; n is 0, 1, or 2; Y is O, S, —NH—, and —N-alkyl-; Ar1 is both 6-membered aromatic rings; Ar2 is 5- or 6-membered aromatic rings with a —NR8R9 group, as defined herein. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions having compounds of formula (I) and methods for using such compounds and compositions.
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Page/Page column 29
(2010/02/12)
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- Copper(II) chloride as an efficient reagent for the dehydrogenation of pyridazinone derivatives
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A new procedure is described for the preparation of pyridazinones from 4,5-dihydropyridazinones under mild conditions with CuCl2 in MeCN via halogenation and spontaneous HCl elimination. For the trans-hexahydrophthalazin-8(1H)-one 1B*, the HCl elimination is five times faster than for the corresponding cis isomer 1B.
- Csende,Szabo,Bernath,Stajer
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p. 1240 - 1242
(2007/10/02)
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- Method for treating anxiety in mammals
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This disclosure describes compositions of matter useful as anxiolytic agents and the method of meliorating anxiety in mammals therewith; the active ingredients of said compositions of matter being certain substituted 6-phenyl-1,2,4-triazolo[4,3-b]pyridazines or the pharmacologically acceptable acid-addition salts thereof.
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- 6-Phenyl-1,2,4-triazolo[4,3-b]pyridazine hypotensive agents
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This disclosure describes novel substituted 6-phenyl-1,2,4-triazolo[4,3-b]pyridazines useful as hypotensive agents.
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- Hypotensive alkyl-3-[6-(aryl)-3-pyridazinyl]-carbazates
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This disclosure describes novel alkyl 3-[6-(aryl)-3-pyridazinyl]-carbazates useful as hypotensive agents in mammals. SP CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation of our copending application Ser. No. 692,254, filed June 3, 1976 now abandoned, which in turn is a continuation-in-part of our abandoned application Ser. No. 552,024, filed Feb. 24, 1975 now abandoned.
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